To analyze the cellular mechanisms responsible for the central nervous system (CNS) autoimmune disease, experimental allergic encephalomyelitis (EAE), factors responsible for activating cells which transfer this disease are examined in vitro. One factor of critical importance is the lymphokine interleukin 2 (IL-2) which regulates proliferation of T-lymphocytes. However, exposure of BP-specific cells to IL-2 alone is not sufficient to insure efficient transfer of EAE; if recipients are also injected with antigen non-specific cells producing the monokine interleukin 1 (IL-1), recipients develop severe EAE. Based on data from in vitro experiments, it appears that the IL-1 producing cells interact with the IL-2-activated, BP-specific cells in vivo. This interaction is required if the proliferating BP-specific cells are to function maximally in vivo and induce severe clinical and histologic EAE. In addition to the inflammatory reaction in the CNS induced by BP-sensitization in acute EAE, demyelination can also be induced in a chronic form of EAE. Our data clearly indicate that the antigen(s) responsible for this demyelination are found in the myelin-fraction of CNS tissue and are separate from the encephalitogenic BP. However, concurrent sensitization with BP and the antigens responsible for demyelination is required to induce in vivo demyelinating lesions in the CNS.